NARP-related alterations in the excitatory and inhibitory circuitry of socially isolated mice: developmental insights and implications for autism spectrum disorder

社会孤立小鼠的兴奋和抑制回路中 NARP 相关改变:发育见解和对自闭症谱系障碍的影响

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作者:Yasunari Yamaguchi #, Kazuya Okamura #, Kazuhiko Yamamuro, Kazuki Okumura, Takashi Komori, Michihiro Toritsuka, Ryohei Takada, Yosuke Nishihata, Daisuke Ikawa, Takahira Yamauchi, Manabu Makinodan, Hiroki Yoshino, Yasuhiko Saito, Hideo Matsuzaki, Toshifumi Kishimoto, Sohei Kimoto

Background

Social isolation during critical periods of development is associated with alterations in behavior and neuronal circuitry. This study aimed to investigate the immediate and developmental effects of social isolation on firing properties, neuronal activity-regulated pentraxin (NARP) and parvalbumin (PV) expression in the prefrontal cortex (PFC), social behavior in juvenile socially isolated mice, and the biological relevance of NARP expression in autism spectrum disorder (ASD).

Conclusion

Our study highlights the role of electrophysiological properties, as well as NARP and PV expression in the PFC in mediating the developmental consequences of social isolation on behavior.

Methods

Mice were subjected to social isolation during postnatal days 21-35 (P21-P35) and were compared with group-housed control mice. Firing properties in the PFC pyramidal neurons were altered in P35 socially isolated mice, which might be associated with alterations in NARP and PV expression.

Results

In adulthood, mice that underwent juvenile social isolation exhibited difficulty distinguishing between novel and familiar mice during a social memory task, while maintaining similar levels of social interaction as the control mice. Furthermore, a marked decrease in NARP expression in lymphoblastoid cell lines derived from adolescent humans with ASD as compared to typically developing (TD) humans was found.

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